title: Cross-reactivities between human IgMs and the four serotypes of dengue virus as probed with artificial homodimers of domain-III from the envelope proteins.
abstract: BACKGROUND
  Dengue fever is the most important vector-borne viral disease. Four serotypes of dengue virus, DENV1 to DENV4, coexist. Infection by one serotype elicits long-lasting immunity to that serotype but not the other three. Subsequent infection by a different serotype is a risk factor for severe dengue. Domain III (ED3) of the viral envelope protein interacts with cell receptors and contains epitopes recognized by neutralizing antibodies. We determined the serotype specificity and cross-reactivity of human IgMs directed against ED3 by using a well-characterized collection of 90 DENV-infected and 89 DENV-uninfected human serums.
  
  
  METHODS
  The recognitions between the four serotypes of ED3 and the serums were assayed with an IgM antibody-capture ELISA (MAC-ELISA) and artificial homodimeric antigens. The results were analyzed with Receiving Operator Characteristic (ROC) curves.
  
  
  RESULTS
  The DENV-infected serums contained IgMs that reacted with one or several ED3 serotypes. The discrimination by ED3 between serums infected by the homotypic DENV and uninfected serums varied with the serotype in the decreasing order DENV1 > DENV2 > DENV3 > DENV4. The ED3 domain of DENV1 gave the highest discrimination between DENV-infected and DENV-uninfected serums, whatever the infecting serotype, and thus behaved like a universal ED3 domain for the detection of IgMs against DENV. Some ED3 serotypes discriminated between IgMs directed against the homotypic and heterotypic DENVs. The patterns of cross-reactivities and discriminations varied with the serotype.
  
  
  CONCLUSIONS
  The results should help better understand the IgM immune response and protection against DENV since ED3 is widely used as an antigen in diagnostic assays and an immunogen in vaccine candidates.
authors.affiliation: Unit of Molecular Prevention and Therapy of Human Diseases, Department of Infection and Epidemiology, Institut Pasteur, Rue du Docteur Roux, F-75015 Paris, France.
authors.forename: Nora
authors.initials: N
authors.lastname: Zidane
authors.forename: Philippe
authors.initials: P
authors.lastname: Dussart
authors.forename: Laetitia
authors.initials: L
authors.lastname: Bremand
authors.forename: Hugues
authors.initials: H
authors.lastname: Bedouelle
mesh_terms: D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D003429:Cross Reactions; D003715:Dengue / Q000276:immunology* / Q000821:virology; D003716:Dengue Virus / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology*; D017434:Protein Structure, Tertiary; D012372:ROC Curve; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D012703:Serotyping; D018709:Statistics, Nonparametric; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D007075:Immunoglobulin M; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins